Experiments are designed to describe biochemical events in the postnatal developing brain of the "phenylketonuric" rat and to relate these changes to behavior. Our working hypothesis is that one or more of the major metabolic products of phenylalanine, produced in large excess in phenylketonuria, may cause the brain dysfunction by arresting neuronal development. Phenylethylamine and its metabolic products, phenylacetic and mandelic acids, and phenylpyruvic acid and its major end product, phenyllactic acid, will be examined individually for effects on myelination and synaptogenesis by biochemical procedures. We will assess the effects of these metabolites derived from phenylalanine on performance in a water maze and an active shock avoidance task. The biochemical mechanism of the brain damage in phenylketonuria will be investigated.